Metabolic Fate and Selective Utilization of Major Fatty Acids in Human Sebaceous Gland

Abstract

The sebaceous gland is an integral part of the pilosebaceous unit of mammalian skin, which produces and secretes a unique mixture of lipids, known as sebum. Wax esters, which account for approximately 25% of human sebaceous lipids, are unique in that they are not synthesized by other cells in the body. To explore the biosynthesis of wax esters, the metabolic fate of exogenously supplied saturated (16:0, 18:0), mono-unsaturated Delta9 (16:1, 18:1), and polyunsaturated (18:2, Delta9,12) fatty acids was followed in biopsy punches from human facial skin rich in sebaceous glands. Acetate was incorporated into all of the cellular and secreted lipids and 16:0 was incorporated into all of the fatty-acid-containing lipids. The 16:0 was elongated to 18:0 and the 16:1 was incorporated primarily into polar lipids, secondarily into triglycerides, but not into other lipids and was elongated to 18:1 (Delta11). As proven by HPTLC analysis, both 18:0 and 18:1 were incorporated into the cellular lipids but at a lower rate into wax esters. Moreover, addition of exogenous 18:1 was not further processed following initial incorporation. Linoleic acid (18:2, Delta9,12) was the only fatty acid tested that appeared to be subjected to beta-oxidation. This was proven to be specific to linoleic acid, as it did not induce the oxidation of other fatty acids. The ability of the sebaceous cells to synthesize wax esters correlated with the beta-oxidation activity in these cells. Thus, the oxidation of linoleic acid is specific for the sebaceous cells and correlates with their function and differentiation. Our results provide evidence that the sebaceous gland selectively utilizes fatty acids as 16:0 is the preferred fatty acid that is incorporated into wax esters and linoleic acid undergoes beta-oxidation.

Beyond acne: Current aspects of sebaceous gland biology and function

“…Through the activation of β-oxidation, linoleic acid is transformed into two-carbon precursors which yields acetyl-CoA, the starter of the biosynthetic pathway, which leads to squalene and wax esters formation [53]. Since linoleic acid is an essential fatty acid, its plasma levels likely regulate its concentration in the sebocytes.…”

“…The identification of the composing species as intact molecules is a suitable analytical approach to find variations in the sebum composition [9,53,54]. Information regarding preferential arrangement of fatty acids in complex lipids can be collected and contribute to the understanding of the role of alterations of sebum composition in the pathologies of the PSU [10].…”

Thematic review series: Skin Lipids. Sebaceous gland lipids: friend or foe?

“…In one study, to determine the fate of circulating lipids, punch biopsies of skin were incubated with radiolabeled palmitic acid, oleic acid, and monounsaturated and polyunsaturated lipids (27). Acetate was incorporated into all of the cellular and secreted lipids, and palmitate was incorporated into all of the fatty acid-containing lipids.…”

The relationship of diet and acne

“…36 The exact fate of these essential nutrients in human sebaceous cells is not yet fully elucidated. An experimental study 37 unveiled a unique metabolic fate of linoleic acid in sebaceous cells, which is preferentially beta-oxidized in contrast to the other predominant fatty acids, which are incorporated to the most prevalent sebaceous lipids. That rapid oxidation and degradation in sebaceous cells allows palmitic acid to be available as the sole substrate to the delta 6 desaturase of sebaceous cells, the predominant desaturase of human sebaceous cells.…”